Volume 128, Issue 2, Pages 351-360 (February 2005) Linkage to peroxisome proliferator-activated receptor-γ in SAMP1/YitFc mice and in human Crohn’s disease  Kazuhiko Sugawara, Timothy S. Olson, Christopher A. Moskaluk, Brian K. Stevens, Sharon Hoang, Kosuke Kozaiwa, Fabio Cominelli, Klaus F. Ley, Marcia McDuffie  Gastroenterology  Volume 128, Issue 2, Pages 351-360 (February 2005) DOI: 10.1053/j.gastro.2004.11.001 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 QTL analysis links susceptibility to chromosome 6. Individual inflammatory indices and the composite total inflammatory score for the (AKR × SAMP1/Fc) backcross cohort (n = 89) were tested for evidence of linkage by a single-point quantitative trait analysis. Levels of significance at the genome-wide level are shown by vertical bars: *P < .37 (suggestive); **P < .05 (significant). ♦, Active index; •, chronic index ▴, epithelial index; ■, total inflammatory score. Regions of conserved synteny with the human genome are shown at the right (filled bars), along with relative locations of selected regional candidate genes (left). Gastroenterology 2005 128, 351-360DOI: (10.1053/j.gastro.2004.11.001) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 Differences in Cdx1 consensus binding sites are associated with altered expression of Pparg1. (A) Sequence analysis of the Pparg1 promoter revealed major differences in spacing among a cluster of Cdx1 consensus binding sites. A putative Nkx-2 binding site in close proximity to the Cdx1 cluster also is shown. A conserved cluster of Cdx1 and Nkx-2 consensus binding sites also was found in the human gene (exon 1, underlined). (B) Left panel, quantitative allele-specific PCR was performed on messenger RNA isolated after careful dissection from associated fat. Data are representative of 2 separate experiments on 2 individual mice from each strain. Right panel, comparable differences also were seen in messenger RNA levels from isolated small intestine epithelial cells from each mouse strain (SAMP1/Fc, N = 3; B6 and AKR, N = 4). Error bars representing 1 SD are shown. Note log10 scale. (C) Representative sections displaying comparable villus architecture (from 3 individual mice in each strain at relevant ages) shows dramatic differences in localization and intensity of Pparγ staining. Gastroenterology 2005 128, 351-360DOI: (10.1053/j.gastro.2004.11.001) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 3 PPARG is associated with CD in human populations. (A) A diagram of the PPARG locus shows the relationship between coding (exons 1–6) and the 5′ untranslated regions of PPARG1 (exons A1, A2) and PPARG2 (exon B), with locations of SNP1–3. (B) Genotype frequencies for individuals carrying the rare variant for SNP1–3: ■, heterozygotes; □, homozygotes. Genotype frequencies did not differ significantly from those expected based on a Hardy–Weinberg distribution (P > .20). Gastroenterology 2005 128, 351-360DOI: (10.1053/j.gastro.2004.11.001) Copyright © 2005 American Gastroenterological Association Terms and Conditions